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[soft music]
[Joey] For life to happen, for basic cellular processes to happen,
that requires cells to build massive
molecular machines.
Our lab is interested in understanding exactly how the cell
puts these things together -- how does it fold the individual
components,
orient them relative to one another,
and allow them to come together to form these machines.
And what I think is really fascinating about this is,
despite the complexity,
you know you have these hundreds of components
coming together, the cell's able to do it rapidly
and efficiently.
My dad worked in construction his whole life.
So I was always around construction
and thinking about how things were built.
I realized that it's just like amazing
what biology is able to build on its own.
And I wanted to learn how it does that.
And as I delved further
and further into the problem it became very clear
that at some fundamental levels we don't
actually understand how biology is able to build
machines like this.
So I did my Ph.D. work here in the
MIT Biology Department in Bob Sauer's lab.
And that's really where I sort of learned
how to do science, it's where I learned all my experimental
work.
And really the people that I got to interact
with and the colleagues that I met while I was
at MIT is what brought me back to try to be part of that
community again.
There's two main complexes that the lab works
on currently. One is the ribosome.
And this is this machine that is
required for all translation in the cell.
And we're interested in understanding exactly
how the ribosome is built.
And the other complex we're interested in is sort of the
other side of proteostasis which is
autophagy. So autophagy is a cellular
homeostasis process that the cell
uses to degrade
damaged or otherwise no longer necessary
organelles.
And we're interested in understanding how it builds the
autophagosome which is the main compartment
it uses to do this degradation.
So it's been really difficult to study this problem historically
in part because we really lack the tools to
look at the assembly intermediates.
One of the things that really excites me about being
at MIT is that we now have access
to electron microscopy.
And this has really been sort of the key that
unlocks this entire world for us.
Cryo-electron microscopy is what allows us to look at a bunch
of intermediates in parallel.
So if we just slow down the process
and we have intermediate sort of all the way along the
pathway, we can put those onto a grid,
image them,
and then try to make sense of how that actually assembles.
How they interconvert?
What's the order of each one of the intermediates that we've
observed?
Typically my lab will set up an experiment where we put
in a block for example by withholding a specific
factor genetically,
or adding a small molecule that we know inhibits that
portion of the process.
What's neat about that is it allows a bunch of intermediates
to accumulate.
And then we can biochemically purify those from the cell.
We'll take that purified material
and we can determine its composition using
mass spectrometry.
That tells us all the proteins that are present
and the abundance of those proteins.
And we can look at the structure of the particles by cryo-electron
microscopy, and that tells us where
those proteins are bound
and in what conformation the entire structure is
formed.
A number of other labs will just focus on using
mass spectrometry,
or just electron microscopy,
or just genetics,
or just biochemistry.
And our hope is to try to integrate all those methods
and give ourselves a holistic view of how the process
happens.
The really long-term goals of the work is to
try to understand how we might intervene
in these processes.
So we think that a number of diseases
are linked to the inability of cells to properly
build autophagosomes
or degrade substrates.
And long-term we'd like to understand
exactly how that breaks down in these diseases,
and then develop pharmacological interventions
to mitigate those diseases.
And then finally this is just sort of a
dark area of biology where we just don't
know what's going on.
And so the hope is that we'll learn more about
how the natural world works by studying these processes.
I think the most amazing thing about MIT
is the community.
It's not the exact equipment
or the buildings, but it's really colleagues
that you're able to run into when you walk down the hall.
And they're excited about their work
and they're excited to talk to you about your
own work. And then also just the fantastic
students that I get to interact
with every day.